Selective organ cooling catheter with guidewire apparatus and temperature-monitoring device

ABSTRACT

A guidable catheter for heating or cooling a surrounding fluid in a feeding vessel in a vasculature of a patient. The catheter includes a heat transfer element, the heat transfer element having a plurality of exterior surface irregularities shaped and arranged to create turbulence in a surrounding fluid. The surface irregularities have a depth at least equal to the boundary layer thickness of flow of the surrounding fluid in the feeding vessel. The catheter assembly also includes a supply catheter having a portion disposed within the heat transfer element to deliver a working fluid to an interior of the heat transfer element. The catheter assembly further includes a return catheter to return a working fluid from the interior of the heat transfer element. A guidewire tube is provided adjacent one of the supply catheter or the return catheter and runs substantially parallel to the axis of the guidable catheter to receive a guidewire disposed within the guidewire tube. The guidable catheter may further have a temperature-monitoring device disposed at the distal tip of the guidewire. The temperature-monitoring device may be a thermocouple or a thermistor. Feedback may further be provided to control the temperature of a source of working fluid. A method is also provided for selectively controlling the temperature of a selected volume of blood in a patient. The method includes introducing a guidewire into a blood vessel feeding a selected volume of blood in a patient and introducing a catheter assembly into the blood vessel feeding a selected volume of blood in a patient by inserting the guidewire into a guidewire tube in the catheter assembly. A working fluid is delivered from a source of working fluid through a supply catheter in the catheter assembly and returned through a return catheter in the catheter assembly. Heat is transferred between a heat transfer element forming a distal end of the catheter assembly and the volume of blood in the feeding vessel. The temperature is monitored of the volume of blood in the feeding vessel by measuring the temperature with a temperature-monitoring device disposed at or near the distal tip of the guidewire.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This is a divisional application of co-pending U.S. patentapplication Ser. No. 09/908,642 filed Jul. 18, 2001, entitled “SelectiveOrgan Cooling Catheter with Guidewire Apparatus andTemperature-Monitoring Device”, which is a continuation patentapplication of U.S. patent application Ser. No.09/262,805 filed on Mar.4, 1999, entitled “A Selective Organ Cooling Catheter with GuidewireApparatus and Temperature-Monitoring Device”, now U.S. Pat. No.6,312,452, which is a continuation-in-part patent application of thefollowing U.S. patent application Ser. Nos.: 09/246,788, filed on Feb.9, 1999, entitled “Method and Device for Applications of Selective OrganCooling”; 09/232,177, filed Jan. 15, 1999, entitled “Method andApparatus for Location and Temperature Specific Drug Action such asThrombolysis”, now U.S. patent No. 6,245,095; 09/215,039, filed Dec. 16,1998, entitled “Method for Low Temperature Thrombolysis and LowTemperature Thrombolytic Agent with Selective Organ TemperatureControl”, now U.S. Pat. No. 6,251,129; 09/215,038, filed Dec. 16, 1999,entitled “Inflatable Catheter for Selective Organ Heating and Coolingand Method of Using the Same”, now U.S. Pat. No. 6,261,312; 09/103,342,filed Jun. 23, 1998, entitled “Selective Organ Cooling Catheter andMethod of Using the Same”, now U.S. Pat. No. 6,096,068; 09/052,545,filed Mar. 31, 1998, entitled “Circulating Fluid Hypothermia Method andApparatus”, now U.S. Pat. No. 6,231,595; 09/047,012, filed Mar. 24,1998, entitled “Selective Organ Hypothermia Method and Apparatus”, nowU.S. Pat. No. 5,957,963, which is a continuation-in-part patentapplication of U.S. patent application Ser. No. 09/012,287, filed Jan.23, 1998, entitled “Selective Organ Hypothermia Method and Apparatus”,now U.S. Pat. No. 6,051,019, all of which are incorporated herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not Applicable

BACKGROUND OF THE INVENTION

[0003] 1. Field of the Invention

[0004] The present invention relates generally to the modification andcontrol of the temperature of a selected body organ. More particularly,the invention relates to guidewire apparatuses which may be employed tolocate selective organ cooling devices at locations of interest, andguidewire apparatuses which may be further employed to determine thelocal temperature of a volume of blood or tissue in which the guidewireis disposed.

[0005] 2. Background Information

[0006] Organs in the human body, such as the brain, kidney and heart,are maintained at a constant temperature of approximately 37° C.Hypothermia can be clinically defined as a core body temperature of 35°C. or less. Hypothermia is sometimes characterized further according toits severity. A body core temperature in the range of 33° C. to 35° C.is described as mild hypothermia. A body temperature of 28° C. to 32° C.is described as moderate hypothermia. A body core temperature in therange of 24° C. to 28° C. is described as severe hypothermia.

[0007] Hypothermia is uniquely effective in reducing brain injury causedby a variety of neurological insults and may eventually play animportant role in emergency brain resuscitation. Experimental evidencehas demonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

[0008] Cerebral hypothermia has traditionally been accomplished throughwhole body cooling to create a condition of total body hypothermia inthe range of 20° C. to 30° C. However, the use of total body hypothermiarisks certain deleterious systematic vascular effects. For example,total body hypothermia may cause severe derangement of thecardiovascular system, including low cardiac output, elevated systematicresistance, and ventricular fibrillation. Other side effects includerenal failure, disseminated intravascular coagulation, and electrolytedisturbances. In addition to the undesirable side effects, total bodyhypothermia is difficult to administer.

[0009] Catheters have been developed which are inserted into thebloodstream of the patient in order to induce total body hypothermia.For example, U.S. Pat. No. 3,425,419 to Data describes a method andapparatus of lowering and raising the temperature of the human body.Data induces moderate hypothermia in a patient using a metalliccatheter. The metallic catheter has an inner passageway through which afluid, such as water, can be circulated. The catheter is insertedthrough the femoral vein and then through the inferior vena cava as faras the right atrium and the superior vena cava. The Data catheter has anelongated cylindrical shape and is constructed from stainless steel. Byway of example, Data suggests the use of a catheter approximately 70 cmin length and approximately 6 mm in diameter. However, use of the Datadevice implicates the negative effects of total body hypothermiadescribed above.

[0010] Due to the problems associated with total body hypothermia,attempts have been made to provide more selective cooling. For example,cooling helmets or headgear have been used in an attempt to cool onlythe head rather than the patient's entire body. However, such methodsrely on conductive heat transfer through the skull and into the brain.One drawback of using conductive heat transfer is that the process ofreducing the temperature of the brain is prolonged. Also, it isdifficult to precisely control the temperature of the brain when usingconduction due to the temperature gradient that must be establishedexternally in order to sufficiently lower the internal temperature. Inaddition, when using conduction to cool the brain, the face of thepatient is also subjected to severe hypothermia, increasing discomfortand the likelihood of negative side effects. It is known that profoundcooling of the face can cause similar cardiovascular side effects astotal body cooling. From a practical standpoint, such devices arecumbersome and may make continued treatment of the patient difficult orimpossible.

[0011] Selected organ hypothermia has been accomplished usingextracorporeal perfusion, as detailed by Arthur E. Schwartz, M. D. etal., in Isolated Cerebral Hypothermia by Single Carotid Artery Perfusionof Extracorporeally Cooled Blood in Baboons, which appeared in Vol. 39,No. 3, NEUROSURGERY 577 (September 1996). In this study, blood wascontinually withdrawn from baboons through the femoral artery. The bloodwas cooled by a water bath and then infused through a common carotidartery with its external branches occluded. Using this method, normalheart rhythm, systemic arterial blood pressure and arterial blood gasvalues were maintained during the hypothermia. This study showed thatthe brain could be selectively cooled to temperatures of 20° C. withoutreducing the temperature of the entire body. However, externalcirculation of blood is not a practical approach for treating humansbecause the risk of infection, need for anticoagulation, and risk ofbleeding is too great. Further, this method requires cannulation of twovessels making it more cumbersome to perform particularly in emergencysettings. Even more, percutaneous cannulation of the carotid artery isdifficult and potentially fatal due to the associated arterial walltrauma. Finally, this method would be ineffective to cool other organs,such as the kidneys, because the feeding arteries cannot be directlycannulated percutaneously.

[0012] Selective organ hypothermia has also been attempted by perfusionof a cold solution such as saline or perflourocarbons. This process iscommonly used to protect the heart during heart surgery and is referredto as cardioplegia. Perfusion of a cold solution has a number ofdrawbacks, including a limited time of administration due to excessivevolume accumulation, cost, and inconvenience of maintaining theperfusate and lack of effectiveness due to the temperature dilution fromthe blood. Temperature dilution by the blood is a particular problem inhigh blood flow organs such as the brain.

BRIEF SUMMARY OF THE INVENTION

[0013] The invention provides a practical method and apparatus whichmodifies and controls the temperature of a selected organ and which maybe used in combination with many complementary therapeutic techniques.

[0014] In one aspect, the invention is directed towards a guidablecatheter for heating or cooling a surrounding fluid in a feeding vesselin a vasculature of a patient. The catheter includes a heat transferelement, the heat transfer element having a plurality of exteriorsurface irregularities shaped and arranged to create turbulence in asurrounding fluid. The surface irregularities have a depth at leastequal to the boundary layer thickness of flow of the surrounding fluidin the feeding vessel. The catheter assembly also includes a supplycatheter having a portion disposed within the heat transfer element todeliver a working fluid to an interior of the heat transfer element. Thecatheter assembly further includes a return catheter to return a workingfluid from the interior of the heat transfer element. A guidewire tubeis provided adjacent one of the supply catheter or the return catheterand runs substantially parallel to the axis of the guidable catheter toreceive a guidewire disposed within the guidewire tube.

[0015] Implementations of the invention may include one or more of thefollowing. The heat transfer element may have coupled thereto at leastone eyelet configured to receive the guidewire threaded therethrough.The heat transfer element may be formed from at least two heat transfersegments, adjacent heat transfer segments joined by bellows or a thintube, and wherein the eyelets are attached to the heat transfer elementat the bellows or thin tube. In the case of a thin tube, the thin tubemay be formed of a metal or a polymeric material. The surfaceirregularities may include a helical ridge and a helical groove formedon each of successive heat transfer segments; the helical ridge on eachheat transfer segment has an opposite helical twist to the helicalridges on adjacent heat transfer segments. The return catheter may becoaxial with the supply catheter, and the return catheter has a largeror smaller radius than the supply catheter. In another aspect, theinvention is directed towards a guidable catheter for heating or coolinga surrounding fluid in a feeding vessel in a vasculature of a patient,and for determining the temperature of a fluid so heated or cooled. Theguidable catheter has the features described above, and further has atemperature-monitoring device disposed at the distal tip of theguidewire. The temperature-monitoring device may be a thermocouple or athermistor. If a thermistor is used, the same may employ a negativetemperature coefficient of resistance. The thermistor may further have aworking element made of ceramic, and may be encapsulated in glass.

[0016] In yet another aspect, the invention is directed toward a deviceincluding a guidable catheter for heating or cooling a surrounding fluidto a predetermined temperature in a feeding vessel in a vasculature of apatient. The device may have the features of the guidable catheterdescribed above and may further include a temperature-monitoring devicedisposed at the distal tip of the guidewire, the temperature monitoringdevice having an output indicative of the sensed temperature. The devicemay further include a temperature-regulated source of working fluidhaving an inlet and an outlet, the supply catheter in pressurecommunication with the inlet and the return catheter in pressurecommunication with the outlet, the source of working fluid having a heatexchange device to change the temperature of the fluid therein uponinput of a signal from the temperature monitoring device.

[0017] In a further aspect, the invention is directed towards a methodfor selectively controlling the temperature of a selected volume ofblood in a patient. The method includes introducing a guidewire into ablood vessel feeding a selected volume of blood in a patient andintroducing a catheter assembly into the blood vessel feeding a selectedvolume of blood in a patient by inserting the guidewire into a guidewiretube in the catheter assembly. A working fluid is delivered from asource of working fluid through a supply catheter in the catheterassembly and returned through a return catheter in the catheterassembly. Heat is transferred between a heat transfer element forming adistal end of the catheter assembly and the volume of blood in thefeeding vessel. The temperature is monitored of the volume of blood inthe feeding vessel by measuring the temperature with atemperature-monitoring device disposed at or near the distal tip of theguidewire.

[0018] Implementations of the invention may include one or more of thefollowing. The method may further include creating turbulence around aplurality of surface irregularities on the heat transfer element at adistance from the heat transfer element greater than the boundary layerthickness of flow in the feeding vessel, thereby creating turbulencethroughout a free stream of blood flow in the feeding vessel. Thesurface irregularities on the heat transfer element may be a pluralityof segments of helical ridges and grooves having alternating directionsof helical rotation. In this case, turbulence is created by establishingrepetitively alternating directions of helical blood flow with thealternating helical rotations of the ridges and grooves. The guidewiremay be inserted through at least one eyelet on the heat transferelement. The method may further include feeding back a signal indicativeof the monitored temperature from the temperature monitoring device tothe source of working fluid to alter the temperature of the workingfluid.

[0019] Advantages of the invention include the following. The inventionprovides a highly efficient device and method for cooling or heatingblood or other bodily fluids, and further provides a device and methodto measure the temperature of the blood or other bodily fluids whosetemperature has been so modified. A signal indicative of the temperaturemeasured may be fed back into a control circuit coupled to a source ofworking fluid to provide an even more accurate control of temperature.The invention further provides a method and device to guide a catheterwith a heat transfer element through tortuous vasculature.

[0020] The novel features of this invention, as well as the inventionitself, will be best understood from the attached drawings, taken alongwith the following description, in which similar reference charactersrefer to similar parts, and in which:

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0021]FIG. 1 is a front view of a first embodiment of a turbulenceinducing heat transfer element according to the principles of theinvention within an artery;

[0022]FIG. 2 is a more detailed front view of the heat transfer elementof FIG. 1;

[0023]FIG. 3 is a front sectional view of the heat transfer element ofFIG. 1;

[0024]FIG. 4 is a transverse sectional view of the heat transfer elementof FIG. 1;

[0025]FIG. 5 is a front perspective view of the heat transfer element ofFIG. 1 in use within a partially broken away blood vessel;

[0026]FIG. 6 is a partially broken away front perspective view of asecond embodiment of a turbulence inducing heat transfer elementaccording to the principles of the invention;

[0027]FIG. 7 is a transverse sectional view of the heat transfer elementof FIG. 6;

[0028]FIG. 8 is a schematic representation of the invention being usedto cool the brain of a patient;

[0029]FIG. 9 is a front sectional view of a guide catheter according toan embodiment of the invention which may be employed for applications ofthe heat transfer element according to the principles of the invention;

[0030]FIG. 10 is a front sectional view of a third embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a return tube/guide catheter;

[0031]FIG. 11 is a front sectional view of a fourth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a delivery catheter;

[0032]FIG. 12 is a front sectional view of the fourth embodiment of FIG.11 further employing a working fluid catheter;

[0033]FIG. 13 is a front sectional view of a fifth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a guidewire;

[0034]FIG. 14 is a front sectional view of a sixth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a delivery / working fluid catheterwith a balloon attachment;

[0035]FIG. 15 is a second front sectional view of the sixth embodimentof FIG. 14 shown with the balloon attachment occluding an opening in theheat transfer element;

[0036]FIG. 16 is a front sectional view of a seventh embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a delivery lumen;

[0037]FIG. 17 is a front sectional view of an eighth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a delivery lumen, this delivery lumennon-coaxial with the central body of the catheter;

[0038]FIG. 18 is a front sectional view of a ninth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing a delivery lumen, this delivery lumennon-coaxial with the central body of the catheter;

[0039]FIG. 19 is a front sectional view of a tenth embodiment of acatheter employing a heat transfer element according to the principlesof the invention further employing multiple lumens;

[0040]FIG. 20 is a cross-sectional view of the tenth embodiment of FIG.19, taken along lines 20-20 of FIG. 19;

[0041]FIG. 21 is a front sectional view of an eleventh embodiment of acatheter employing a heat transfer element according to the principlesof the invention;

[0042]FIG. 22 is a side sectional view of a further embodiment of theinvention featuring an embodiment of a guidewire apparatus which may beemployed to maneuver the catheter into a predetermined position;

[0043]FIG. 23 is a side section view of a further embodiment of theinvention featuring an embodiment of a temperature monitoring device, inthe form of a thermocouple, which may be employed to determine the localtemperature of a volume of blood or tissue in which the guidewire islocated; and

[0044]FIG. 24 is a side section view of a further embodiment of theinvention featuring an embodiment of a temperature monitoring device, inthe form of a thermistor, which may be employed to determine the localtemperature of a volume of blood or tissue in which the guidewire islocated.

[0045]FIG. 25 is a schematic diagram of an embodiment of the inventionshowing a feedback loop to a temperature-controlled source of workingfluid.

DETAILED DESCRIPTION OF THE INVENTION

[0046] The temperature of a selected organ may be intravascularlyregulated by a heat transfer element placed in the organ's feedingartery to absorb or deliver heat to or from the blood flowing into theorgan. While the method is described with respect to blood flow into anorgan, it is understood that heat transfer within a volume of tissue isanalogous. In the latter case, heat transfer is predominantly byconduction.

[0047] The heat transfer may cause either a cooling or a heating of theselected organ. A heat transfer element that selectively alters thetemperature of an organ should be capable of providing the necessaryheat transfer rate to produce the desired cooling or heating effectwithin the organ to achieve a desired temperature.

[0048] The heat transfer element should be small and flexible enough tofit within the feeding artery while still allowing a sufficient bloodflow to reach the organ in order to avoid ischemic organ damage. Feedingarteries, like the carotid artery, branch off the aorta at variouslevels. Subsidiary arteries continue to branch off these initialbranches. For example, the internal carotid artery branches off thecommon carotid artery near the angle of the jaw. The heat transferelement is typically inserted into a peripheral artery, such as thefemoral artery, using a guide catheter or guidewire (see below), andaccesses a feeding artery by initially passing though a series of one ormore of these branches. Thus, the flexibility and size, e.g., thediameter, of the heat transfer element are important characteristics.This flexibility is achieved as is described in more detail below.

[0049] These points are illustrated using brain cooling as an example.The common carotid artery supplies blood to the head and brain. Theinternal carotid artery branches off the common carotid artery to supplyblood to the anterior cerebrum. The heat transfer element may be placedinto the common carotid artery or into both the common carotid arteryand the internal carotid artery.

[0050] The benefits of hypothermia described above are achieved when thetemperature of the blood flowing to the brain is reduced to between 30°C. and 32° C. A typical brain has a blood flow rate through each carotidartery (right and left) of approximately 250-375 cubic centimeters perminute (cc/min). With this flow rate, calculations show that the heattransfer element should absorb approximately 75-175 watts of heat whenplaced in one of the carotid arteries to induce the desired coolingeffect. Smaller organs may have less blood flow in their respectivesupply arteries and may require less heat transfer, such as about 25watts.

[0051] The method employs conductive and convective heat transfers. Oncethe materials for the device and a working fluid are chosen, theconductive heat transfers are solely dependent on the temperaturegradients. Convective heat transfers, by contrast, also rely on themovement of fluid to transfer heat. Forced convection results when theheat transfer surface is in contact with a fluid whose motion is induced(or forced) by a pressure gradient, area variation, or other such force.In the case of arterial flow, the beating heart provides an oscillatorypressure gradient to force the motion of the blood in contact with theheat transfer surface. One of the aspects of the device uses turbulenceto enhance this forced convective heat transfer.

[0052] The rate of convective heat transfer Q is proportional to theproduct of S , the area of the heat transfer element in direct contactwith the fluid, ΔT=T_(b)−T_(s), the temperature differential between thesurface temperature T_(s), of the heat transfer element and the freestream blood temperature T_(b), and {overscore (h)}_(c), the averageconvection heat transfer coefficient over the heat transfer area.{overscore (h)}_(c) is sometimes called the “surface coefficient of heattransfer” or the “convection heat transfer coefficient”.

[0053] The magnitude of the heat transfer rate Q to or from the fluidflow can be increased through manipulation of the above threeparameters. Practical constraints limit the value of these parametersand how much they can be manipulated. For example, the internal diameterof the common carotid artery ranges from 6 to 8 mm. Thus, the heattransfer element residing therein may not be much larger than 4 mm indiameter to avoid occluding the vessel. The length of the heat transferelement should also be limited. For placement within the internal andcommon carotid artery, the length of the heat transfer element islimited to about 10 cm. This estimate is based on the length of thecommon carotid artery, which ranges from 8 to 12 cm.

[0054] Consequently, the value of the surface area S is limited by thephysical constraints imposed by the size of the artery into which thedevice is placed. Surface features, such as fins, can be used toincrease the surface area of the heat transfer element, however, thesefeatures alone cannot provide enough surface area enhancement to meetthe required heat transfer rate to effectively cool the brain.

[0055] One may also attempt to vary the magnitude of the heat transferrate by varying ΔT. The value of ΔT=T_(b)−T₈, can be varied by varyingthe surface temperature T_(s), of the heat transfer element. Theallowable surface temperature of the heat transfer element is limited bythe characteristics of blood. The blood temperature is fixed at about37° C., and blood freezes at approximately 0° C. When the bloodapproaches freezing, ice emboli may form in the blood which may lodgedownstream, causing serious ischemic injury. Furthermore, reducing thetemperature of the blood also increases its viscosity which results in asmall decrease in the value of {overscore (h)}_(c). Increased viscosityof the blood may further result in an increase in the pressure dropwithin the artery, thus compromising the flow of blood to the brain.Given the above constraints, it is advantageous to limit the surfacetemperature of the heat transfer element to approximately 1° C.-5° C.,thus resulting in a maximum temperature differential between the bloodstream and the heat transfer element of approximately 32° C.-36° C.

[0056] One may also attempt to vary the magnitude of the heat transferrate by varying {overscore (h)}_(c). Fewer constraints are imposed onthe value of the convection heat transfer coefficient {overscore(h)}_(c). The mechanisms by which the value of {overscore (h)}_(c), maybe increased are complex. However, one way to increase {overscore(h)}_(c), for a fixed mean value of the velocity is to increase thelevel of turbulent kinetic energy in the fluid flow.

[0057] The heat transfer rate Q_(no-flow) in the absence of fluid flowis proportional to ΔT, the temperature differential between the surfacetemperature T_(s) of the heat transfer element and the free stream bloodtemperature T_(b) times k, the diffusion constant, and is inverselyproportion to δ, the thickness of the boundary layer.

[0058] The magnitude of the enhancement in heat transfer by fluid flowcan be estimated by taking the ratio of the heat transfer rate withfluid flow to the heat transfer rate in the absence of fluid flowN=Q_(flow)/Q_(no-flow)={overscore (h)}_(c)/(k/δ). This ratio is calledthe Nusselt number (“Nu”). For convective heat transfer between bloodand the surface of the heat transfer element, Nusselt numbers of 30-80have been found to be appropriate for selective cooling applications ofvarious organs in the human body. Nusselt numbers are generallydependent on several other numbers: the Reynolds number, the Womersleynumber, and the Prandtl number.

[0059] Stirring-type mechanisms, which abruptly change the direction ofvelocity vectors, may be utilized to induce turbulent kinetic energy andincrease the heat transfer rate. The level of turbulence so created ischaracterized by the turbulence intensity Θ. Turbulence intensity Θ isdefined as the root mean square of the fluctuating velocity divided bythe mean velocity. Such mechanisms can create high levels of turbulenceintensity in the free stream, thereby increasing the heat transfer rate.This turbulence intensity should ideally be sustained for a significantportion of the cardiac cycle, and should ideally be created throughoutthe free stream and not just in the boundary layer.

[0060] Turbulence does occur for a short period in the cardiac cycleanyway. In particular, the blood flow is turbulent during a smallportion of the descending systolic flow. This portion is less than 20%of the period of the cardiac cycle. If a heat transfer element is placedco-axially inside the artery, the heat transfer rate will be enhancedduring this short interval. For typical of these fluctuations, theturbulence intensity is at least 0.05. In other words, the instantaneousvelocity fluctuations deviate from the mean velocity by at least 5%.Although ideally turbulence is created throughout the entire period ofthe cardiac cycle, the benefits of turbulence are obtained if theturbulence is sustained for 75%, 50% or even as low as 30% or 20% of thecardiac cycle.

[0061] One type of turbulence-inducing heat transfer element which maybe advantageously employed to provide heating or cooling of an organ orvolume is described in co-pending U.S. patent application Ser. No.09/103,342 to Dobak and Lasheras for a “Selective Organ Cooling Catheterand Method of Using the Same,” incorporated by reference above. In thatapplication, and as described below, the heat transfer element is madeof a high thermal conductivity material, such as metal. The use of ahigh thermal conductivity material increases the heat transfer rate fora given temperature differential between the coolant within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant within the heat transfer element, allowing safercoolants, such as water, to be used. Highly thermally conductivematerials, such as metals, tend to be rigid. In that application,bellows provided a high degree of articulation that compensated for theintrinsic stiffness of the metal. In another application incorporated byreference above, the bellows are replaced with a straight metal tubehaving a predetermined thickness to allow flexibility via bending of themetal. Alternatively, the bellows may be replaced with a polymer tube,e.g., a latex rubber tube, a plastic tube, or a flexible plasticcorrugated tube.

[0062] The device size may be minimized, e.g., less than 4 mm, toprevent blockage of the blood flowing in the artery. The design of theheat transfer element should facilitate flexibility in an inherentlyinflexible material.

[0063] To create the desired level of turbulence intensity in the bloodfree stream during the whole cardiac cycle, one embodiment of the deviceuses a modular design. This design creates helical blood flow andproduces a high level of turbulence in the free stream by periodicallyforcing abrupt changes in the direction of the helical blood flow. FIG.1 is a perspective view of such a turbulence inducing heat transferelement within an artery. Turbulent flow would be found at point 114, inthe free stream area. The abrupt changes in flow direction are achievedthrough the use of a series of two or more heat transfer segments, eachcomprised of one or more helical ridges. To affect the free stream, thedepth of the helical ridge is larger than the thickness of the boundarylayer which would develop if the heat transfer element had a smoothcylindrical surface.

[0064] The use of periodic abrupt changes in the helical direction ofthe blood flow in order to induce strong free stream turbulence may beillustrated with reference to a common clothes washing machine. Therotor of a washing machine spins initially in one direction causinglaminar flow. When the rotor abruptly reverses direction, significantturbulent kinetic energy is created within the entire wash basin as thechanging currents cause random turbulent motion within the clothes-waterslurry.

[0065] In the following description, the term “pressure communication”is used to describe a situation between two points in a flow or in astanding fluid. If pressure is applied at one point, the second pointwill eventually feel effects of the pressure if the two points are inpressure communication. Any number of valves or elements may be disposedbetween the two points, and the two points may still be in pressurecommunication if the above test is met. For example, for a standingfluid in a pipe, any number of pipe fittings may be disposed between twopipes and, so long as an open path is maintained, points in therespective pipes may still be in pressure communication.

[0066]FIG. 2 is an elevation view of one embodiment of a heat transferelement 14. The heat transfer element 14 is comprised of a series ofelongated, articulated segments or modules 20, 22, 24. Three suchsegments are shown in this embodiment, but two or more such segmentscould be used. As seen in FIG. 2, a first elongated heat transfersegment 20 is located at the proximal end of the heat transfer element14. A turbulenc-einducing exterior surface of the segment 20 comprisesfour parallel helical ridges 28 with four parallel helical grooves 26therebetween. One, two, three, or more parallel helical ridges 28 couldalso be used. In this embodiment, the helical ridges 28 and the helicalgrooves 26 of the heat transfer segment 20 have a left hand twist,referred to herein as a counter-clockwise spiral or helical rotation, asthey proceed toward the distal end of the heat transfer segment 20.

[0067] The first heat transfer segment 20 is coupled to a secondelongated heat transfer segment 22 by a first tube section 25, whichprovides flexibility. The second heat transfer segment 22 comprises oneor more helical ridges 32 with one or more helical grooves 30therebetween. The ridges 32 and grooves 30 have a right hand, orclockwise, twist as they proceed toward the distal end of the heattransfer segment 22. The second heat transfer segment 22 is coupled to athird elongated heat transfer segment 24 by a second tube section 27.The third heat transfer segment 24 comprises one or more helical ridges36 with one or more helical grooves 34 therebetween. The helical ridge36 and the helical groove 34 have a left hand, or counter-clockwise,twist as they proceed toward the distal end of the heat transfer segment24. Thus, successive heat transfer segments 20, 22, 24 of the heattransfer element 14 alternate between having clockwise andcounterclockwise helical twists. The actual left or right hand twist ofany particular segment is immaterial, as long as adjacent segments haveopposite helical twist.

[0068] In addition, the rounded contours of the ridges 28, 32, 36 alsoallow the heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall. A heat transfer element may be comprised of two, three, ormore heat transfer segments.

[0069] The tube sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidthat is cycled through the heat transfer element 14. The structure ofthe tube sections 25, 27 allows them to bend, extend and compress, whichincreases the flexibility of the heat transfer element 14 so that it ismore readily able to navigate through blood vessels. The tube sections25, 27 are also able to tolerate cryogenic temperatures without a lossof performance. The tube sections 25, 27 may have a predeterminedthickness of their walls, such as between about 0.5 and 0.8 mils. Thepredetermined thickness is to a certain extent dependent on the diameterof the overall tube. Thicknesses of 0.5 to 0.8 mils may be appropriateespecially for a tubal diameter of about 4 mm. For smaller diameters,such as about 3.3 mm, larger thicknesses may be employed for higherstrength. In another embodiment, tube sections 25, 27 may be formed froma polymer material such as rubber, e.g., latex rubber.

[0070] The exterior surfaces of the heat transfer element 14 can be madefrom metal except in flexible joint embodiments where the surface may becomprised of a polymer material. The metal may be a very high thermalconductivity material such as nickel, thereby facilitating efficientheat transfer. Alternatively, other metals such as stainless steel,titanium, aluminum, silver, copper and the like, can be used, with orwithout an appropriate coating or treatment to enhance biocompatibilityor inhibit clot formation. Suitable biocompatible coatings include,e.g., gold, platinum or polymer paralyene. The heat transfer element 14may be manufactured by plating a thin layer of metal on a mandrel thathas the appropriate pattern. In this way, the heat transfer element 14may be manufactured inexpensively in large quantities, which is animportant feature in a disposable medical device.

[0071] Because the heat transfer element 14 may dwell within the bloodvessel for extended periods of time, such as 24-48 hours or even longer,it may be desirable to treat the surfaces of the heat transfer element14 to avoid clot formation. One means by which to prevent thrombusformation is to bind an antithrombogenic agent to the surface of theheat transfer element 14. For example, heparin is known to inhibit clotformation and is also known to be useful as a biocoating. Alternatively,the surfaces of the heat transfer element 14 may be bombarded with ionssuch as nitrogen. Bombardment with nitrogen can harden and smooth thesurface and, thus prevent adherence of clotting factors to the surface.

[0072]FIG. 3 is a longitudinal sectional view of the heat transferelement 14, taken along line 3-3 in FIG. 2. Some interior contours areomitted for purposes of clarity. An inner tube 42 creates an innercoaxial lumen 40 and an outer coaxial lumen 46 within the heat transferelement 14. Once the heat transfer element 14 is in place in the bloodvessel, a working fluid such as saline or other aqueous solution may becirculated through the heat transfer element 14. Fluid flows up a supplycatheter into the inner coaxial lumen 40. At the distal end of the heattransfer element 14, the working fluid exits the inner coaxial lumen 40and enters the outer lumen 46. As the working fluid flows through theouter lumen 46, heat is transferred between the working fluid and theexterior surface 37 of the heat transfer element 14. Because the heattransfer element 14 is constructed from a high conductivity material,the temperature of its exterior surface 37 may reach very close to thetemperature of the working fluid. The tube 42 may be formed as aninsulating divider to thermally separate the inner lumen 40 from theouter lumen 46. For example, insulation may be achieved by creatinglongitudinal air channels in the wall of the insulating tube 42.Alternatively, the insulating tube 42 may be constructed of anon-thermally conductive material like polytetrafluoroethylene or someother polymer.

[0073] It is important to note that the same mechanisms that govern theheat transfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid whichremains a liquid as the coolant. Other coolants such as freon undergonucleate boiling and create turbulence through a different mechanism.Saline is a safe coolant because it is non-toxic, and leakage of salinedoes not result in a gas embolism, which could occur with the use ofboiling refrigerants. Since turbulence in the coolant is enhanced by theshape of the interior surface 38 of the heat transfer element 14, thecoolant can be delivered to the heat transfer element 14 at a warmertemperature and still achieve the necessary heat transfer rate.

[0074] This has a number of beneficial implications in the need forinsulation along the catheter shaft length. Due to the decreased needfor insulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

[0075]FIG. 4 is a transverse sectional view of the heat transfer element14, taken at a location denoted by the line 4-4 in FIG. 2. FIG. 4illustrates a five-lobed embodiment, whereas FIG. 2 illustrates afour-lobed embodiment. As mentioned earlier, any number of lobes mightbe used. In FIG. 4, the coaxial construction of the heat transferelement 14 is clearly shown. The inner coaxial lumen 40 is defined bythe insulating coaxial tube 42. The outer lumen 46 is defined by theexterior surface of the insulating coaxial tube 42 and the interiorsurface 38 of the heat transfer element 14. In addition, the helicalridges 32 and helical grooves 30 may be seen in FIG. 4. As noted above,in the preferred embodiment, the depth of the grooves, d₃ is greaterthan the boundary layer thickness which would have developed if acylindrical heat transfer element were introduced. For example, in aheat transfer element 14 with a 4 mm outer diameter, the depth of theinvaginations, d₃ may be approximately equal to 1 mm if designed for usein the carotid artery. Although FIG. 4 shows four ridges and fourgrooves, the number of ridges and grooves may vary. Thus, heat transferelements with 1, 2, 3, 4, 5, 6, 7, 8 or more ridges are specificallycontemplated.

[0076]FIG. 5 is a perspective view of a heat transfer element 14 in usewithin a blood vessel, showing only one helical lobe per segment forpurposes of clarity. Beginning from the proximal end of the heattransfer element (not shown in FIG. 5), as the blood moves forwardduring the systolic pulse, the first helical heat transfer segment 20induces a counter-clockwise rotational inertia to the blood. As theblood reaches the second segment 22, the rotational direction of theinertia is reversed, causing turbulence within the blood. Further, asthe blood reaches the third segment 24, the rotational direction of theinertia is again reversed. The sudden changes in flow direction activelyreorient and randomize the velocity vectors, thus ensuring turbulencethroughout the bloodstream. During turbulent flow, the velocity vectorsof the blood become more random and, in some cases, become perpendicularto the axis of the artery. In addition, as the velocity of the bloodwithin the artery decreases and reverses direction during the cardiaccycle, additional turbulence is induced and turbulent motion issustained throughout the duration of each pulse through the samemechanisms described above.

[0077] Thus, a large portion of the volume of warm blood in the vesselis actively brought in contact with the heat transfer element 14, whereit can be cooled by direct contact rather than being cooled largely byconduction through adjacent laminar layers of blood. As noted above, thedepth of the grooves 26, 30, 34 (FIG. 2) is greater than the depth ofthe boundary layer that would develop if a straight-walled heat transferelement were introduced into the blood stream. In this way, free streamturbulence is induced. In the preferred embodiment, in order to createthe desired level of turbulence in the entire blood stream during thewhole cardiac cycle, the heat transfer element 14 creates a turbulenceintensity greater than about 0.05. The turbulence intensity may begreater than 0.05, 0.06, 0.07 or up to 0.10 or 0.20 or greater.

[0078] Referring back to FIG. 2, the heat transfer element 14 has beendesigned to address all of the design criteria discussed above. First,the heat transfer element 14 is flexible and is made of a highlyconductive material. The flexibility is provided by a segmentaldistribution of tube sections 25, 27 which provide an articulatingmechanism. The tube sections have a predetermined thickness whichprovides sufficient flexibility. Second, the exterior surface area 37has been increased through the use of helical ridges 28, 32, 36 andhelical grooves 26, 30, 34. The ridges also allow the heat transferelement 14 to maintain a relatively atraumatic profile, therebyminimizing the possibility of damage to the vessel wall. Third, the heattransfer element 14 has been designed to promote turbulent kineticenergy both internally and externally. The modular or segmental designallows the direction of the invaginations to be reversed betweensegments. The alternating helical rotations create an alternating flowthat results in a mixing of the blood in a manner analogous to themixing action created by the rotor of a washing machine that switchesdirections back and forth. This mixing action is intended to promotehigh level turbulent kinetic energy to enhance the heat transfer rate.The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

[0079]FIG. 6 is a cut-away perspective view of an alternative embodimentof a heat transfer element 50. An external surface 52 of the heattransfer element 50 is covered with a series of axially staggeredprotrusions 54. The staggered nature of the outer protrusions 54 isreadily seen with reference to FIG. 7 which is a transversecross-sectional view taken at a location denoted by the line 7-7 in FIG.6. In order to induce free stream turbulence, the height, dp, of thestaggered outer protrusions 54 is greater than the thickness of theboundary layer which would develop if a smooth heat transfer element hadbeen introduced into the blood stream. As the blood flows along theexternal surface 52, it collides with one of the staggered protrusions54 and a turbulent wake flow is created behind the protrusion. As theblood divides and swirls along side of the first staggered protrusion54, its turbulent wake encounters another staggered protrusion 54 withinits path preventing the re-lamination of the flow and creating yet moreturbulence. In this way, the velocity vectors are randomized andturbulence is created not only in the boundary layer but also throughoutthe free stream. As is the case with the preferred embodiment, thisgeometry also induces a turbulent effect on the internal coolant flow.

[0080] A working fluid is circulated up through an inner coaxial lumen56 defined by an insulating coaxial tube 58 to a distal tip of the heattransfer element 50. The working fluid then traverses an outer coaxiallumen 60 in order to transfer heat to the exterior surface 52 of theheat transfer element 50. The inside surface of the heat transferelement 50 is similar to the exterior surface 52, in order to induceturbulent flow of the working fluid. The inner protrusions can bealigned with the outer protrusions 54, as shown in FIG. 7, or they canbe offset from the outer protrusions 54, as shown in FIG. 6.

[0081]FIG. 8 is a schematic representation of the invention being usedto cool the brain of a patient. The selective organ hypothermiaapparatus shown in FIG. 8 includes a working fluid supply 10, preferablysupplying a chilled liquid such as water, alcohol or a halogenatedhydrocarbon, a supply catheter 12 and the heat transfer element 14. Thesupply catheter 12 has a coaxial construction. An inner coaxial lumenwithin the supply catheter 12 receives coolant from the working fluidsupply 10. The coolant travels the length of the supply catheter 12 tothe heat transfer element 14 which serves as the cooling tip of thecatheter. At the distal end of the heat transfer element 14, the coolantexits the insulated interior lumen and traverses the length of the heattransfer element 14 in order to decrease the temperature of the heattransfer element 14. The coolant then traverses an outer lumen of thesupply catheter 12 so that it may be disposed of or recirculated. Thesupply catheter 12 is a flexible catheter having a diameter sufficientlysmall to allow its distal end to be inserted percutaneously into anaccessible artery such as the femoral artery of a patient as shown inFIG. 8. The supply catheter 12 is sufficiently long to allow the heattransfer element 14 at the distal end of the supply catheter 12 to bepassed through the vascular system of the patient and placed in theinternal carotid artery or other small artery. The method of insertingthe catheter into the patient and routing the heat transfer element 14into a selected artery is well known in the art.

[0082] Although the working fluid supply 10 is shown as an exemplarycooling device, other devices and working fluids may be used. Forexample, in order to provide cooling, freon, perflourocarbon, water, orsaline may be used, as well as other such coolants.

[0083] The heat transfer element can absorb or provide over 75 Watts ofheat to the blood stream and may absorb or provide as much as 100 Watts,150 Watts, 170 Watts or more. For example, a heat transfer element witha diameter of 4 mm and a length of approximately 10 cm using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2 atmospherescan absorb about 100 Watts of energy from the bloodstream. Smallergeometry heat transfer elements may be developed for use with smallerorgans which provide 60 Watts, 50 Watts, 25 Watts or less of heattransfer.

[0084] The practice of the present invention is illustrated in thefollowing non-limiting example.

Exemplary Procedure

[0085] 1. The patient is initially assessed, resuscitated, andstabilized.

[0086] 2. The procedure is carried out in an angiography suite orsurgical suite equipped with fluoroscopy.

[0087] 3. Because the catheter is placed into the common carotid artery,it is important to determine the presence of stenotic atheromatouslesions. A carotid duplex (Doppler/ultrasound) scan can quickly andnon-invasively make this determination. The ideal location for placementof the catheter is in the left carotid so this may be scanned first. Ifdisease is present, then the right carotid artery can be assessed. Thistest can be used to detect the presence of proximal common carotidlesions by observing the slope of the systolic upstroke and the shape ofthe pulsation. Although these lesions are rare, they could inhibit theplacement of the catheter. Examination of the peak blood flow velocitiesin the internal carotid can determine the presence of internal carotidartery lesions. Although the catheter is placed proximally to suchlesions, the catheter may exacerbate the compromised blood flow createdby these lesions. Peak systolic velocities greater that 130 cm/sec andpeak diastolic velocities>100cm/sec in the internal indicate thepresence of at least 70% stenosis. Stenosis of 70% or more may warrantthe placement of a stent to open up the internal artery diameter.

[0088] 4. The ultrasound can also be used to determine the vesseldiameter and the blood flow and the catheter with the appropriatelysized heat transfer element could be selected.

[0089] 5. After assessment of the arteries, the patients inguinal regionis sterilely prepped and infiltrated with lidocaine.

[0090] 6. The femoral artery is cannulated and a guidewire may beinserted to the desired carotid artery. Placement of the guidewire isconfirmed with fluoroscopy.

[0091] 7. An angiographic catheter can be fed over the wire and contrastmedia injected into the artery to further to assess the anatomy of thecarotid.

[0092] 8. Alternatively, the femoral artery is cannulated and a 10-12.5french (f) introducer sheath is placed.

[0093] 9. A guide catheter is placed into the desired common carotidartery. If a guiding catheter is placed, it can be used to delivercontrast media directly to further assess carotid anatomy.

[0094] 10. A 10f-12f (3.3-4.0 mm) (approximate) cooling catheter issubsequently filled with saline and all air bubbles are removed.

[0095] 11. The cooling catheter is placed into the carotid artery viathe guiding catheter or over the guidewire. Placement is confirmed withfluoroscopy.

[0096] 12. Alternatively, the cooling catheter tip is shaped (angled orcurved approximately 45 degrees), and the cooling catheter shaft hassufficient pushability and torqueability to be placed in the carotidwithout the aid of a guidewire or guide catheter.

[0097] 13. The cooling catheter is connected to a pump circuit alsofilled with saline and free from air bubbles. The pump circuit has aheat exchange section that is immersed into a water bath and tubing thatis connected to a peristaltic pump. The water bath is chilled toapproximately 0°C.

[0098] 14. Cooling is initiated by starting the pump mechanism. Thesaline within the cooling catheter is circulated at 5 cc/sec. The salinetravels through the heat exchanger in the chilled water bath and iscooled to approximately 1° C.

[0099] 15. The saline subsequently enters the cooling catheter where itis delivered to the heat transfer element. The saline is warmed toapproximately 5-7° C. as it travels along the inner lumen of thecatheter shaft to the end of the heat transfer element.

[0100] 16. The saline then flows back through the heat transfer elementin contact with the inner metallic surface. The saline is further warmedin the heat transfer element to 12-15° C., and in the process, heat isabsorbed from the blood, cooling the blood to 30° C. to 32° C.

[0101] 17. The chilled blood then goes on to chill the brain. It isestimated that 15-30 minutes will be required to cool the brain to 30 to32° C.

[0102] 18. The warmed saline travels back down the outer lumen of thecatheter shaft and back to the chilled water bath where it is cooled to1° C.

[0103] 19. The pressure drops along the length of the circuit areestimated to be 2-3atmospheres.

[0104] 20. The cooling can be adjusted by increasing or decreasing theflow rate of the saline. Monitoring of the temperature drop of thesaline along the heat transfer element will allow the flow to beadjusted to maintain the desired cooling effect.

[0105] 21. The catheter is left in place to provide cooling for 12 to 24hours.

[0106] 22. If desired, warm saline can be circulated to promote warmingof the brain at the end of the procedure.

[0107] The invention may also be used in combination with othertechniques. For example, one technique employed to place working lumensor catheters in desired locations employs guide catheters, as mentionedabove. Referring to FIG. 9, a guide catheter 102 is shown which may beadvantageously employed in the invention. A description below, inconnection with FIG. 22 et seq., describes an alternate embodiment ofthe invention employing a guidewire apparatus.

[0108] The guide catheter 102 has a soft tapered tip 104 and a retainingflange 124 at a distal end 101. The soft tapered tip 104 allows anatraumatic entrance of the guide catheter 102 into an artery as well asa sealing function as is described in more detail below. The retainingflange 124 may be a metallic member adhered to the guide catheterinterior wall or may be integral with the material of the tube. Theretaining flange 124 further has a sealing function described in moredetail below.

[0109] The guide catheter 102 may have various shapes to facilitateplacement into particular arteries. In the case of the carotid artery,the guide catheter 102 may have the shape of a hockey stick. The guidecatheter 102 may include a Pebax® tube with a Teflon®liner. The Teflon®liner provides sufficient lubricity to allow minimum friction whencomponents are pushed through the tube. A metal wire braid may also beemployed between the Pebax® tube and the Teflon® liner to providetorqueability of the guide catheter 102.

[0110] A number of procedures may be performed with the guide catheter102 in place within an artery. For example, a stent may be disposedacross a stenotic lesion in the internal carotid artery. This procedureinvolves placing a guidewire through the guide catheter 102 and acrossthe lesion. A balloon catheter loaded with a stent is then advancedalong the guidewire. The stent is positioned across the lesion. Theballoon is expanded with contrast, and the stent is deployedintravascularly to open up the stenotic lesion. The balloon catheter andthe guidewire may then be removed from the guide catheter.

[0111] A variety of treatments may pass through the guide catheter. Forexample, the guide catheter, or an appropriate lumen disposed within,may be employed to transfer contrast for diagnosis of bleeding orarterial blockage, such as for angiography. The same may further beemployed to deliver various drug therapies, e.g., to the brain. Suchtherapies may include delivery of thrombolytic drugs that lyse clotslodged in the arteries of the brain, as are further described in anapplication incorporated by reference above.

[0112] A proximal end 103 of the guide catheter 102 has a male luerconnector for mating with a y-connector 118 attached to a supply tube108. The supply tube 108 may include a braided Pebax® tube or apolyimide tube. The y-connector 118 connects to the guide catheter 102via a male/female luer connector assembly 116. The y-connector 118allows the supply tube 108 to enter the assembly and to pass through themale/female luer connector assembly 116 into the interior of the guidecatheter 102. The supply tube 108 may be disposed with an outlet at itsdistal end. The outlet of the supply tube 108 may also be used toprovide a working fluid to the interior of a heat transfer element 110.The guide catheter 102 may be employed as the return tube for theworking fluid supply in this aspect of the invention. In thisembodiment, a heat transfer element 110 is delivered to the distal end101 of the guide catheter 102 as is shown in FIG. 10.

[0113] In FIG. 10, the heat transfer element 110 is shown, nearly in aworking location, in combination with the return tube/guide catheter102. In particular, the heat transfer element 110 is shown near thedistal end 101 of the return tube/guide catheter (“RTGC”) 102. The heattransfer element 110 may be kept in place by a flange 106 on the heattransfer element 110 that abuts the retaining flange 124 on the RTGC102. Flanges 124 and 106 may also employ o-rings such as an o-ring 107shown adjacent to the flange 106. Other such sealing mechanisms ordesigns may also be used. In this way, the working fluid is preventedfrom leaking into the blood.

[0114] The supply tube 108 may connect to the heat transfer element 110(the connection is not shown) and may be employed to push the heattransfer element 110 through the guide catheter 102. The supply tubeshould have sufficient rigidity to accomplish this function. In analternative embodiment, a guidewire may be employed having sufficientrigidity to push both the supply tube 108 and the heat transfer element110 through the guide catheter 102. So that the supply tube 108 ispreventing from abutting its outlet against the interior of the heattransfer element 110 and thereby stopping the flow of working fluid, astrut 112 may be employed on a distal end of the supply tube 108. Thestrut 112 may have a window providing an alternative path for theflowing working fluid.

[0115] The heat transfer element 110 may employ any of the formsdisclosed above, as well as variations of those forms. For example, theheat transfer element 110 may employ alternating helical ridgesseparated by flexible joints, the ridges creating sufficient turbulenceto enhance heat transfer between a working fluid and blood in theartery. Alternatively, the heat transfer element 110 may be inflatableand may have sufficient surface area that the heat transfer due toconduction alone is sufficient to provide the requisite heat transfer.Details of the heat transfer element 110 are omitted in FIG. 10 forclarity.

[0116]FIG. 11 shows an alternate embodiment of the invention in which aheat transfer element 204 employs an internal supply catheter 216. Theheat transfer element 204 is shown with turbulence-inducinginvaginations 218 located thereon. Similar invaginations may be locatedin the interior of the heat transfer element 204 but are not shown forclarity. Further, it should be noted that the heat transfer element 204is shown with merely four invaginations. Other embodiments may employmultiple elements connected by flexible joints as is disclosed above. Asingle heat transfer element is shown in FIG. 11 merely for clarity.

[0117] A return supply catheter 202 is shown coupled to the heattransfer element 204. The return supply catheter may be coupled to theheat transfer element 204 in known fashion, and may provide a convenientreturn path for working fluid as may be provided to the heat transferelement 204 to provide temperature control of a flow or volume of blood.

[0118] A delivery catheter 216 is also shown in FIG. 11. The deliverycatheter 216 may be coupled to a y-connector at its proximal end in themanner disclosed above. The delivery catheter 216 may be freely disposedwithin the interior of the return supply catheter 202 except where it isrestrained from further longitudinal movement (in one direction) by aretaining flange 210 disposed at the distal end 208 of the heat transferelement 204. The delivery catheter 216 may be made sufficiently flexibleto secure itself within retaining flange 210, at least for a shortduration. The delivery catheter 216 may have a delivery outlet 212 at adistal end to allow delivery of a drug or other such material fortherapeutic purposes. For example, a radio-opaque fluid may be dispensedfor angiography or a thrombolytic drug for thrombolysis applications.

[0119] For applications in which it is desired to provide drainage ofthe artery, e.g., laser ablation, the delivery catheter may be pulledupstream of the retaining flange 210, exposing an annular hole in fluidcommunication with the return supply catheter 202. The return supplycatheter 202 may then be used to drain the volume adjacent the retainingflange 210.

[0120] The assembly may also perform temperature control of blood in theartery where the same is located. Such temperature control proceduresmay be performed, e.g., before or after procedures involving thedelivery catheter 216. Such a device for temperature control is shown inFIG. 12. In this figure, a working fluid catheter 222 is disposed withinthe return supply catheter 202 and the heat transfer element 204. In amanner similar to the delivery catheter 216, the working fluid cathetermay be freely disposed within the interior of the return supply catheter202 and may further be coupled to a y-connector at its proximal end inthe manner disclosed above. The working fluid catheter 222 may furtherbe made sufficiently flexible to secure itself within retaining flange210, at least for a short duration. The working fluid catheter 222 mayhave a plurality of outlets 214 to allow delivery of a working fluid.The outlets 214 are located near the distal end 224 of the working fluidcatheter 222 but somewhat upstream. In this way, the outlets 214 allowdispensation of a working fluid into the interior of the heat transferelement 204 rather than into the blood stream. The working fluidcatheter 222 may also be insulated to allow the working fluid tomaintain a desired temperature without undue heat losses to the walls ofthe working fluid catheter 222.

[0121] One way of using the same catheter as a delivery catheter and asa working fluid catheter is shown in FIGS. 14 and 15. In FIG. 14, adelivery/working fluid catheter 248 is shown in a position similar tothe respective catheters of FIGS. 11 and 12. The delivery/working fluidcatheter 248 has working fluid outlets and a delivery outlet, and isfurther equipped with a balloon 244 disposed at the distal end. Balloon244 may be inflated with a separate lumen (not shown). By retracting thedelivery/working fluid catheter 248 to the position shown in FIG. 15,the balloon 244 may be made to seal the hole defined by retaining flange210, thereby creating a fluid-tight seal so that working fluid may bedispensed from outlets 246 to heat or cool the heat transfer element204.

[0122] One method of disposing a heat transfer device within a desiredartery, such as the carotid artery, involves use of a guidewire.Referring to FIG. 13, a guidewire 232 is shown disposed within theinterior of the heat transfer element 204. The heat transfer element 204may conveniently use the hole defined by retaining flange 210 to bethreaded onto the guidewire 232. A separate embodiment of the invention,also employing a guidewire, is described below in connection with FIG.22 et seq.

[0123] Numerous other therapies may then employ the return supplycatheter and heat transfer element as a “guide catheter”. For example,various laser and ultrasound ablation catheters may be disposed within.In this way, these therapeutic techniques may be employed at nearly thesame time as therapeutic temperature control, including, e.g.,neuroprotective cooling.

[0124] The use of an additional lumen was disclosed above in connectionwith passing a variety of treatments through the guide catheter. Forexample, an additional lumen may be employed to transfer contrast fordiagnosis of bleeding or arterial blockage, such as for angiography.Such an additional lumen may be defined by a drug delivery catheterwhich forms an integral or at least integrated part of the overallinventive catheter assembly. The same may be employed to deliver variousdrug therapies, e.g., to the brain. The use of an additional lumen wasfurther mentioned in connection with expansion of a balloon that may beused to occlude a drug delivery lumen outlet.

[0125]FIG. 16 depicts an implementation of an embodiment of theinvention employing just such a third lumen. In FIG. 16, a third lumen316 is a small central lumen defined by a drug delivery cathetersubstantially coaxial with the supply and return catheters. A returncatheter 302 defining an outlet lumen 320 is coupled to a heat transferelement 304 as before. The heat transfer element 304 may haveturbulence-inducing invaginations 306 thereon. Within the heat transferelement 304 and the return catheter 302 is an inlet lumen 318 defined bya supply catheter 310. The inlet lumen 318 may be used to deliver aworking fluid to the interior of the heat transfer element 304. Theoutlet lumen 320 may be used to return or exhaust the working fluid fromthe heat transfer element 304. As above, their respective functions mayalso be reversed. The radius of the return catheter may be greater orless than the radius of the supply catheter. The working fluid may beused to heat or cool the heat transfer element which in turn heats orcools the fluid surrounding the heat transfer element.

[0126] A drug delivery catheter 312 defines the third lumen 316 and asshown may be coaxial with the inlet lumen 318 and the outlet lumen 320.Of course, the delivery catheter 312 may be also be off-axis ornon-coaxial with respect to the inlet lumen 318 and the outlet lumen320.

[0127] For example, as shown in FIG. 17, the drug delivery catheter maybe a lumen 316′ within the return catheter and may be further defined bya catheter wall 312′. As another example, as shown in FIG. 18, the drugdelivery catheter may be a lumen 316″ adjacent to and parallel to thereturn catheter and may be further defined by a catheter wall 312″. Inan alternative embodiment, more than one lumen may be provided withinthe return catheter to allow delivery of several types of products,e.g., thrombolytics, saline solutions, etc. Of course, the supplycatheter may also be used to define the drug delivery catheter. The drugdelivery catheter may be substantial coaxial with respect to the returncatheter or supply catheter or both, or may alternatively be off-axis.The drug delivery catheter includes an outlet at a distal end thereof.The outlet may be distal or proximal of the distal end of the return orsupply catheters. The outlet may be directed parallel to the return orsupply catheters or may alternatively be directed transverse of thereturn or supply catheters.

[0128] The device may be inserted in a selected feeding vessel in thevascular system of a patient. For example, the device may be inserted inan artery which feeds a downstream organ or which feeds an artery which,in turn, feeds a downstream organ. In any of the embodiments of FIGS.16-18, the drug delivery catheter lumen may be used to deliver a drug,liquid, or other material to the approximate location of the heattransfer element. Such delivery may occur before, after, orcontemporaneous with heat transfer to or from the blood. In this way,drugs or enzymes which operate at temperatures other than normal bodytemperature may be used by first altering the local blood temperaturewith the heat transfer element and then delivering the temperaturespecific drug, such as a temperature specific thrombolytic, which thenoperates at the altered temperature. Alternatively, such “third” lumens(with the supply and return catheters for the working fluid defining“first” and “second” lumens) may be used to remove particles, debris, orother desired products from the blood stream.

[0129]FIGS. 19 and 20 show another embodiment of the invention that isrelated to the embodiment of FIG. 17. In this embodiment, severaladditional sealed lumens are disposed in the return catheter. Some ofthe lumens may be for drug delivery and others may be used to enhanceturbulence in a manner described below. The sealed lumens are inpressure communication with a supply of air to inflate the same. In FIG.19, a return catheter 302′ has one lumen 316′″ C as shown for drugdelivery. Another, lumen 316′″ I, is shown which may be employed toalter the geometry and shape of the overall catheter. That is, inflatinglumen 316′″ I causes the lumen to expand in the same way that inflatinga balloon causes it to expand. In order to allow for the expansion,appropriately reduced return catheter wall thicknesses may be employed.Also, inflatable lumens 316′″ A-B and 316′″ D-N may be distributed in asubstantially symmetric fashion around the circumference of the catheterfor a uniform inflation if desired. Of course, less distortion underinflation may occur at or adjacent lumens such as 316′″ C used for drugdelivery, as these do not inflate.

[0130] The inflatable lumens 316′″ A-B and 316″′ D-N may be caused toinflate under influence of, e.g., an air compressor with a variable airdelivery flow. Rapid pulses of air may be used to inflate the lumens316′″ A-B and 316′″ D-N in a rapid and repeated fashion. By so doing,the outer walls defining these lumens move rapidly into and out of thebloodstream around the catheter, inducing turbulence. Preferably, theamplitude of the vibrations is large enough to move the outer wallsdefining the lumens out of the boundary layer and into the free streamof blood. This effect produces turbulence which is used to enhance heattransfer. As it is important to induce turbulence only near the heattransfer element, the area of appropriate wall thickness to allow forinflation need only be at, near, or adjacent the portion of the returncatheter exterior wall adjacent the heat transfer element. In otherwords, the return catheter wall only requires reduction near the heattransfer element. The remainder of the catheter wall may remain thickfor strength and durability.

[0131] The supply catheter 310 may be constructed such that the samedoes not contact the interior of the distal end 308 of the heat transferelement, which may cause a subsequent stoppage of flow of the workingfluid. Such construction may be via struts located in the returncatheter 302 that extend radially inwards and secure the supply catheter310 from longitudinal translations. Alternatively, struts may extendlongitudinally from the distal end of the supply catheter 310 and holdthe same from contacting the heat transfer element. This construction issimilar to strut 112 shown in FIG. 10.

[0132]FIG. 21 shows an alternate method of accomplishing this goal. InFIG. 21, a heat transfer element 304′ has an orifice 326 at a distal end308. A supply catheter 310′ is equipped with a drug delivery catheter312′ extending coaxially therein. The drug delivery catheter 312 may beformed of a solid material integral with supply catheter 310′, or thetwo may be bonded after being constructed of separate pieces, or the twomay remain separate during use, with a friction fit maintaining theirpositions with respect to each other. The supply catheter 310′ is “inposition” when a tapered portion 324 of the same is lodged in the hole326 in the heat transfer element 304′. The tapered portion 324 should belodged tightly enough to cause a strong friction fit so that workingfluid does not leak through the hole 326. However, the tapered portion324 should be lodged loosely enough to allow the supply catheter 310′ tobe removed from the heat transfer element 304′ if continued independentuse of the return catheter is desired.

[0133] The supply catheter 310′ has a plurality of outlets 322. Outlets322 are provided at points generally near or adjacent the distal end ofthe supply catheter 310′. The outlets are provided such that, when thesupply catheter 310′ is in position, the outlets generally face the heattransfer element 304′. In this way, the working fluid, emerging from theoutlets 322, more directly impinges on the interior wall of the heattransfer element 304′. In particular, the working fluid exits theinterior of the supply catheter and flows into a volume defined by theexterior of the supply catheter and the interior of the heat transferelement.

[0134] For clarity, FIG. 21 does not show the invaginations on theinterior wall of the heat transfer element 304′. However, it will beunderstood that such invaginations may be present and may allow forenhanced heat transfer in combination with the emerging working fluid.

[0135] In the embodiments of FIGS. 9, 11, and 13-21, various types ofcatheter assemblies employing drug delivery catheters are described. Inthose embodiments, and particularly in the embodiments such as FIGS. 11,14-16 and 21, in which a distal end of the drug delivery catheterprotrudes substantially from the distal end of the remainder of thecatheter assembly, a therapy may be performed in which the distal end ofthe catheter is embedded into a clot to be dissolved. An enzymesolution, such as a warm or cool enzyme solution, may then be sentdirectly into the clot to locally enhance the fibrinolytic activity.

[0136] In particular, the catheter may be placed as described above. Inthis procedure, however, the catheter is placed such that the tip of theprotruding drug delivery catheter touches, is substantially near, orbecomes embedded within the clot. An enzyme solution or other such drugis then delivered down the drug delivery catheter directly into the clotor into the volume of blood surrounding the clot. The enzyme solutionmay include tPA, streptokinase, urokinase, pro-urokinase, combinationsthereof, and may be heated to enhance fibrinolytic activity. In arelated embodiment, the solution may be a simple heated saline solution.The heated saline solution warms the clot, or the volume surrounding theclot, again leading to enhanced fibrinolytic activity.

[0137] In these procedures, it is advantageous to use embodiments of theinvention in which the distal tip of the drug delivery catheter issubstantially protruding, or is distal, from the remainder of thecatheter assembly. In this way, the distal tip may be disposed adjacentto or within a clot without being obstructed by the remainder of thecatheter assembly.

[0138] As mentioned above, the catheter and heat transfer element may beconveniently disposed in a predetermined position using a guidecatheter. The predetermined position may be one in which blood flowspast the heat transfer element towards an organ to be cooled. FIG. 13shows one such embodiment in which a guidewire passes down the center ofthe heat transfer element.

[0139]FIG. 22 shows a related embodiment of a cooling device including aguidewire apparatus. Referring to FIG. 22, a cooling device includes acatheter 400 and a heat transfer element 401, both shown incross-section. The catheter 400 is coupled to the heat transfer element401 via a mount 410. Mount 410 may be an adhesive material, afriction-fit, a snap-fit, or other such techniques or devices as areknown in the art, etc. At least two lumens run the length of thecatheter 400 and heat transfer element 401: an inlet lumen 402 definedby an inlet tube 405 and an outlet lumen 407 defined by an outlet orreturn tube 404. A guidewire lumen 403 is defined by guidewire lumen406. Guidewire lumen 406 may be employed to maneuver the cooling devicealong a guidewire 408. It is noted here that guidewire 408 may itself bea microcatheter useful for delivering drugs or other such therapies.

[0140] The heat transfer element 401 is also shown schematically in FIG.22. Various details have been omitted for clarity. In the figure, theheat transfer element 401 is formed from successive segments.Alternating helices, forming invaginations, are shown by elements 412,412′, 412″, and 412′″. The elements shown in FIG. 22 are not perfecthelices, but are intended to demonstrate how such elements may beconfigured in the system. As can be seen, the helicity may alternatebetween successive adjacent segments to enhance turbulence and thus heattransfer.

[0141] Adjacent segments may be coupled by thin tubes of metal orpolymeric materials, or alternatively by metal bellows. Elements 414,414′, 414″ are schematic in nature and are intended to demonstrate thelocation of such coupling segments.

[0142] An optional feature which may be employed is a spring-tip 434.The spring-tip 434 is a tightly wound spring of small radius whichallows the cooling device to navigate tortuous vasculature easily andwithout damage to vessel walls.

[0143] At various locations, an eyelet or equivalent structure may beprovided through which a guidewire may pass. The eyelet or equivalentstructures need not be employed on the catheter 400, as the guidewirelumen 403 serves this purpose. However, the eyelet or equivalentstructures may be especially advantageously provided on the heattransfer element and/or on the spring-tip 434. A break-out of the eyeletstructure is shown in FIG. 22. In the break-out drawing, a portion of abellows 414 is shown supporting an eyelet mount 422. Mount 422 may thensupport eyelet 424 through which guidewire 408 passes. Of course, aneyelet 424 is not the only type of structure which may be employed:fork-type structures or other similar guiding structures may also beemployed. Similar considerations hold for the eyelet structures422′/424′, 422″/424″, and 438/436 (the latter at the end of thespring-tip 434).

[0144] In use, the guidewire 408 is placed into the vasculature of apatient. For an application of brain cooling, the guidewire may be runfrom the femoral artery through the vasculature into the internalcarotid artery. The heat transfer element 401 may then be threaded ontothe guidewire 408 by first threading eyelet 438 onto the guidewire 408.One or more of eyelets 424″, 424′, and 424 may then be threaded onto theguidewire 408 successively. Finally, the guidewire 408 may be runthrough the guidewire lumen 403 (defined by guidewire tube 406). Thecooling device, defined by catheter 400 and heat transfer element 401,may then be inserted into the patient's vasculature along the pathdefined by the guidewire 408. The applications of the cooling device,which may alternatively provide heating rather than cooling, arediscussed above.

[0145] The tip of the guidewire 408 may contain or be part of atemperature monitor. The temperature monitor may be employed to measurethe temperature upstream or downstream of the heat transfer element andcatheter, depending on the direction of blood flow relative to thetemperature monitor. The temperature monitor may be, e.g., athermocouple or thermistor.

[0146] An embodiment of the invention employing a thermocouple is shownin FIG. 23. In this figure, a thermocouple 440 is mounted on the end ofthe guidewire 408. For the temperatures considered in blood heating orcooling, most of the major thermocouple types may be used, includingTypes T, E, J, K, G, C, D, R, S, B.

[0147] In an alternative embodiment, a thermistor may be used as shownin FIG. 24. The figure shows a thermistor device 441 attached to the endof the guidewire 408. Thermistors are thermally-sensitive resistorswhose resistance changes with a change in body temperature. The use ofthermistors may be particularly advantageous for use intemperature-monitoring of blood flow past cooling devices because oftheir sensitivity. For temperature monitoring of body fluids,thermistors that are mostly commonly used include those with a largenegative temperature coefficient of resistance (“NTC”). These shouldideally have a working temperature range inclusive of 25° C. to 40° C.Potential thermistors that may be employed include those with activeelements of polymers or ceramics. Ceramic thermistors may be mostpreferable as these may have the most reproducible temperaturemeasurements. Most thermistors of appropriate sizes are encapsulated inprotective materials such as glass. The size of the thermistor, forconvenient mounting to the guidewire and for convenient insertion in apatient's vasculature, may be about or less than 15 mils. Largerthermistors may be used where desired. Of course, various othertemperature-monitoring devices may also be used as dictated by the size,geometry, and temperature resolution desired.

[0148] A signal from the temperature monitoring device may be fed backto the source of working fluid to control the temperature of the workingfluid emerging therefrom. Referring to FIG. 25, such a feedback signal458 is shown. In particular, FIG. 25 shows schematically the catheterconnected to a source of working fluid 452. As is obvious, the aspectratio of the catheter shown is highly atypical and is shown in thisfashion solely for clarity. The figure shows that a proximal end ofsupply lumen 402 defined by supply tube 405 is connected at an outputport 454 to the source of working fluid 452. The return lumen 407defined by the tube 404 is similarly connected at an input port 460 tothe source of working fluid 452. The source of working fluid 452 cancontrol the temperature of the working fluid emerging from the outputport 454. A signal from a circuit 458 may be inputted to the source ofworking fluid 452 at an input 456. The signal from circuit 458 may befrom the thermocouple 440, or may alternatively be from any other typeof temperature-monitoring device, such as at the tip of the guidewire408.

[0149] The signal may advantageously be employed to alter thetemperature, if necessary, of the working fluid from the source 452. Forexample, if the temperature-monitoring device senses that thetemperature of the blood flowing in the feeding vessel of the patient'svasculature is below optimal, a signal may be sent to the source ofworking fluid 452 to increase the temperature of the working fluidemerging therefrom. The opposite may be performed if thetemperature-monitoring device senses that the temperature of the bloodflowing in the feeding vessel of the patient's vasculature is aboveoptimal.

[0150] The invention has been described with respect to certainembodiments. It will be clear to one of skill in the art that variationsof the embodiments may be employed in the method of the invention.Accordingly, the invention is limited only by the scope of the appendedclaims.

What is claimed is:
 1. A temperature monitoring device assembly,comprising: an elongated catheter having a distal end and a proximalend, the catheter being configured for advancing the catheter into apatient with the distal end located in the patient's body and theproximal end located outside the patient's body; at least onetemperature monitoring device located at or near the distal end of theprobe body generating respective at least one temperature signal; acatheter connector located at or near the proximal end of the catheter;and a cable having a cable connector configured for engaging thecatheter connector and at least one controller electrically connected tothe cable connector.
 2. The probe of claim 1, wherein the catheter isconfigured for advancement into a patient's vasculature.
 3. The assemblyof claim 1, wherein the temperature monitoring device includes athermistor and the probe body is dosposable.
 4. The probe of claim 1, incombination with the controller, wherein the temperature monitoringdevice generates a control feedback signal useful by the controller forcontrolling a heat exchanger.
 5. The combination of claim 4, in furthercombination with the heat exchanger.
 6. The combination of claim 5, infurther combination with a heat exchange catheter in closed loop fluidcommunication with the heat exchanger.
 7. A controller including aprogram of instructions undertaking method acts for controlling a heatexchanger, the method acts comprising: receiving, from a temperaturesensor, a patient temperature signal; controlling a heat exchanger for acooling catheter in response to the signal; and generating an alarmsignal when the signal reaches a predetermined setpoint.
 8. Thecontroller of claim 7, wherein the method further comprises generatingan alarm signal when the signal indicates a failure of the sensor.